HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 582/3/1027    most recent jphysiol.2007.132308v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nielsen, D. K. Articles by Simonsen, L. O. Search for Related Content PubMed PubMed Citation Articles by Nielsen, D. K. Articles by Simonsen, L. O. Related Collections Neuroscience

¹ August Krogh Institute, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen Ø, Denmark

The labelling pattern of cellular phosphoinositides (PtdInsP_n) was studied in Ehrlich ascites cells labelled in vivo for 24 h with myo-[2-³H]- or L-myo-[1-³H]inositol and exposed to anisotonic or isosmotic volume perturbations. In parallel experiments the cell volume ([¹⁴C]3-OMG space) was monitored. In hypotonic media the cells initially swelled osmotically and subsequently as expected showed a regulatory volume decrease (RVD) response. Concurrently, the cell content of PtdInsP₂ showed a marked, transient decrease and the content of PtdInsP a small, transient increase. The changes in PtdInsP₂ and PtdInsP content increased progressively with the extent of hypotonicity (in the range 1.00–0.50 relative osmolarity). No evidence was found for either hydrolysis of PtdInsP₂ or formation of PtdInsP₃. In hypertonic medium (relative osmolarity 1.50), cells initially shrank osmotically and subsequently as expected showed a small regulatory volume increase (RVI) response. Concurrently, the cell content of PtdInsP₂ showed a marked increase and the content of PtdInsP a small decrease, i.e. changes in the opposite direction of those seen in hypotonic media. In isosmotic media with high (100 mM) or low (0.8 mM) K⁺ concentration, cells slowly swelled or shrank due to uptake or loss of isosmotic KCl. Under these conditions, with largely unchanged intracellular ionic strength, the cell content of PtdInsP₂ and PtdInsP remained constant. Our results show that PtdInsP₂ is not volume sensitive per se, and moreover that the regulatory volume adjustments in Ehrlich ascites cells are not mediated by PtdInsP₂ hydrolysis and its subsequent production of second messengers. The simplest interpretation of the observed effects would be that PtdInsP₂ is controlled by ionic strength, probably via activation/inhibition of phosphoinositide-specific phosphatases/kinases. In Ehrlich ascites cells, as shown previously, the opposing ion channels and transporters activated during RVD and RVI, respectively, are controlled with tight negative coordination by a common cell volume ‘set-point’ that is shifted in anisotonic media, but unchanged during cell swelling in isosmotic high K⁺ medium. We hypothesize that PtdInsP₂ might orchestrate this ‘set-point’ shift.

(Received 14 March 2007; accepted after revision 6 June 2007; first published online 7 June 2007)
Corresponding author L. O. Simonsen: August Krogh Institute, University of Copenhagen, 13 Universitetsparken, DK-2100 Copenhagen Ø, Denmark. Email: losimonsen{at}aki.ku.dk

This article has been cited by other articles:

				M. Rasmussen, R. T. Alexander, B. V. Darborg, N. Mobjerg, E. K. Hoffmann, A. Kapus, and S. F. Pedersen Osmotic cell shrinkage activates ezrin/radixin/moesin (ERM) proteins: activation mechanisms and physiological implications Am J Physiol Cell Physiol, January 1, 2008; 294(1): C197 - C212. [Abstract] [Full Text] [PDF]

				B. Robertson Regulation of ion channels and transporters by phosphatidylinositol 4,5-bisphosphate J. Physiol., August 1, 2007; 582(3): 901 - 902. [Full Text] [PDF]